Furthermore, the autophagy induction was also characteristic hallmark of amyloid-beta-induced cytotoxicity. Morphological changes were positively correlated with the extent of phosphorylated glycogen synthase kinase-3 beta (phospho-Tyr(216)-GSK-3 beta, GSK-3 beta-P(Y216)). The activity of GSK-3 beta is believed to cause tau protein hyper-phosphorylation, increased amyloid-beta production and local plaque-associated microglial-mediated inflammatory responses. All of them are symptomatic for AD. In our studies, the highly significant Y216 phosphorylation and over-expression of total GSK-3 beta were observed in A beta PPsw-transfected PC12 cells. In addition, the immuocytochemical

analysis S63845 showed co-localization of GSK-3 beta-P(Y216) see more and amyloid-beta deposits. Thus, our data support a functional role of GSK-3 beta in A beta PP

processing, further implicating this kinase in the amyloid-beta-dependent pathogenesis. (C) 2009 Elsevier Inc. All rights reserved.”
“Extinction of fear requires learning that anticipated aversive events no longer occur. Animal models reveal that sustained phosphorylation of the extracellular signal-regulated kinase (Erk) in hippocampal CA1 neurons plays an important role in this process. However, the key signals triggering and regulating the activity of Erk are not known. By varying the degree of expected and delivered aversive

reinforcement, we demonstrate that Erk specifically responds to prediction errors of contextual aversive events. An increase of somatonuclear phospho-Erk (pErk) within principal CA1 neurons was observed only when the expectation of contextual Selleck ARS-1620 foot shock was violated, but not when the context was consistently nonreinforced or reinforced by foot shock. The rate of error detection, Erk signaling, and fear extinction markedly depended on shock expectancy and the aversive valence of the context, as revealed by comparison of groups trained with single, continuous, or partial reinforcement. On the basis of these findings, the hippocampal Erk response to prediction errors of aversive outcome is proposed as a unique mechanism of fear extinction. Improving the detection and processing of these errors has the potential to attenuate fear responses in patients with anxiety disorders.”
“Cadmium, mercury and rotenone are environmental pollutants whose neurotoxic mechanisms are not fully understood. We have shown previously that exposure of nerve cells to these agents produces oxidative stress which reversibly blocks growth factor and cytokine-mediated Janus kinase (Jak)/signal transducer and activator of transcription (STAT) signaling. Here we determined a critical role for mitochondrial dysfunction in inhibiting Jak/STAT activity in human BE(2)-C neuroblastoma cells.